Hope and help for triple-negative (TNBC) and other forms of hormone-negative breast cancer.

Thursday, January 17, 2013

Scientists Map TNBC's Metastatic Path

Cancer Scientists at Weill Cornell Medical College have discovered the molecular switch that allows triple negative breast cancer cells to grow the amoeba-like protrusions they need to crawl away from a primary tumor and metastasize throughout the body. Their findings, published in Cancer Cell, suggest a novel approach for developing agents to treat cancer once it has spread."Metastasis can be lethal, and our findings point to potential targeted treatments to stop the spread of this aggressive breast cancer," says the study's senior investigator, Vivek Mittal, MD, an associate professor of cell and developmental biology and director of the Lehman Brothers Lung Cancer Laboratory at Weill Cornell Medical College. According to researchers, if such agents were developed, they would perhaps be the first to specifically treat cancer metastasis in patients whose tumors have already spread. They would also be among the first designed to restore the function of a microRNA (miRNA), a small, non-coding RNA that regulates gene expression, which is crucial to cancer spread. While distinct miRNA "signatures" have been found for many tumor types, including different breast cancers, their specific roles in later steps of cancer metastasis has been unclear, Dr. Mittal says.In the study, researchers set out to identify a miRNA that impacts metastasis without affecting primary tumor growth, as well as address its underlying molecular mechanisms and therapeutic potential against metastatic breast cancer. They discovered that a miRNA known as miR-708 is inhibited in metastatic triple negative breast cancer. They found that miR-708 acts as a metastatic tumor inhibitor, and when its function is restored, the tumors do not spread or form lethal macrometastases. Using genome wide miRNA sequencing, Dr. Mittal and his research team found in human samples of triple negative breast cancer that miR-708 was significantly down-regulated with its normal expression curtailed. In both laboratory cells and in animal studies, the researchers identified that the normal role of miR-708 is to suppress the protein neuronatin, which is located on the membrane of a cell's endoplasmic reticulum—an organelle that stores calcium. Neuronatin helps control how much calcium leaves that organelle. "It is calcium that provides legs to cancer cells to help them escape a tumor. So miR-708 acts as a suppressor of metastasis by keeping neuronatin in check," Dr. Mittal says. "If miR-708 is itself suppressed, there is an increase in production of neuronatin proteins, which then allows more calcium to leave the endoplasmic reticulum and activate a cascade of genes that turn on migratory pathways leading to metastasis."Researchers found that delivering synthetic miR-708, carried by bubbles of fat, blocked metastatic outgrowth of triple negative breast cancer cells in the lung of mice. This makes miR-708 a promising therapeutic against metastatic breast cancer.The researchers also discovered that polycomb repressor complex proteins are responsible for silencing miR-708. These proteins remodel the way DNA is packaged in order to epigenetically silence genes. Dr. Mittal adds that the findings suggest that pharmacological agents now being tested in lymphoma cancer cells may also help to restore miR-708 in triple negative breast cancer. These drugs are designed to inhibit histone-lysine N-methyltransferase EZH2, the member of the polycomb group that directly silences miR-708."These study results are terrific," says co-author Dr. Linda Vahdat, director of the Breast Cancer Research Program, chief of the Solid Tumor Service and professor of medicine at Weill Cornell Medical College and medical oncologist at the Iris Cantor Women's Health Center at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. "It not only offers us an avenue to treat metastatic triple negative breast cancer in the short-term, but also gives us the roadmap to prevent metastases in the long-run. We are anxious to get this into the clinic and are working as quickly as possible towards that end."

No comments:

DONATE

Please help support this blog. All donations go to time and resources to maintain this rich source of information about triple-negative breast cancer.

Donate in the name of a friend or family member with breast cancer and I'll send a personal note of encouragement to her or him.

NOTE: I am all out of books, so I can no longer send them as part of the donation.

Surviving Triple-Negative Breast Cancer: Hope, Treatment, Recovery

Finally! A book about TNBC written by a woman who's been through it—Patricia Prijatel, founder and editor of this blog. If you like this blog, you'll love this book.

Patricia Prijatel

Founder of Positives About Negative and author of Surviving Triple Negative Breast Cancer

Top Cancer Blog

From Symphony Sisterhood

Welcome

When I was diagnosed with hormone-receptor-negative breast cancer, I required a positive attitude of myself—I was not going to let a disease have the upper hand. I hope I can share some at that attitude with you while I offer what I have learned in my trek through this disease as a patient and medical writer.

It's a given that life ends in death. Cancer just makes you face that inevitability more directly than you might have before. To me, that means living fully right now.

Three Mountain Dogs, a children's book by Patricia Prijatel

Triple-negative breast cancer (TNBC) lacks hormone receptors for estrogen, progesterone, and Her2/neu. It affects about 20 percent of all those with breast cancer. This blog offers information and hope for those with TNBC and other forms of hormone-negative breast cancer.

Calm Spirit Note Cards

Blank greeting cards with the Calm Spirit image are available in packets of 6. They're ideal for sending a personal message of encouragement to anyone living with cancer. Boxes of six are available for $10.00 and can be ordered by contacting my friend Madlyn at madlyn.ferraro@ gmail com. Individual cards are $2.50 each.